TY - JOUR
T1 - Regorafenib plus Nivolumab in Patients with Advanced Gastric or Colorectal Cancer
T2 - An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603)
AU - Fukuoka, Shota
AU - Hara, Hiroki
AU - Takahashi, Naoki
AU - Kojima, Takashi
AU - Kawazoe, Akihito
AU - Asayama, Masako
AU - Yoshii, Takako
AU - Kotani, Daisuke
AU - Tamura, Hitomi
AU - Yuichi Mikamoto, BPharm
AU - Hirano, Nami
AU - Wakabayashi, Masashi
AU - Nomura, Shogo
AU - Sato, Akihiro
AU - Kuwata, Takeshi
AU - Togashi, Yosuke
AU - Nishikawa, Hiroyoshi
AU - Shitara, Kohei
N1 - Funding Information:
Supported by Bayer HealthCare Pharmaceuticals Inc and Ono Pharmaceuticals. The funders of the study had no role in study design; data collection, analysis, or interpretation; or writing of the report.
Publisher Copyright:
© 2020 by American Society of Clinical Oncology
PY - 2020/4/28
Y1 - 2020/4/28
N2 - PURPOSE This is a phase Ib trial of regorafenib plus nivolumab for gastric and colorectal cancer. PATIENTS AND METHODS Enrolled patients received regorafenib plus nivolumab in a dose-finding part to estimate the maximum tolerated dose. Additional patients were enrolled in a dose-expansion part. Regorafenib of 80-160 mg was administered once daily for 21 days on/7 days off with nivolumab 3 mg/kg every 2 weeks. The primary end point was dose-limiting toxicity (DLT) during the first 4 weeks to estimate the recommended dose. RESULTS Fifty patients (25 each with gastric and colorectal cancer) were enrolled. All patients had received $ 2 previous lines of chemotherapy, including anti-angiogenetic inhibitors in 96% of patients. Seven patients with gastric cancer had previously been treated with immune checkpoint inhibitors. One patient had microsatellite instability–high colorectal cancer, whereas the remaining patients had microsatellite stable or mismatch repair–proficient tumors. Three DLTs (grade 3 colonic perforation, maculopapular rash, and proteinuria) were observed with regorafenib 160 mg; none were observed with 80 or 120 mg. During the dose-expansion part, regorafenib dose was reduced from 120 to 80 mg because of frequent maculopapular rash. The common grade $ 3 treatment-related adverse events were rash (12%), proteinuria (12%), and palmar-plantar erythrodysesthesia (10%). Objective tumor response was observed in 20 patients (40%), including 11 with gastric cancer (44%) and 9 with colorectal cancer (36%). Median progression-free survival was 5.6 and 7.9 months in patients with gastric and colorectal cancer, respectively. CONCLUSION The combination of regorafenib 80 mg plus nivolumab had a manageable safety profile and encouraging antitumor activity in patients with gastric and colorectal cancer, which warrants additional investigations in larger cohorts.
AB - PURPOSE This is a phase Ib trial of regorafenib plus nivolumab for gastric and colorectal cancer. PATIENTS AND METHODS Enrolled patients received regorafenib plus nivolumab in a dose-finding part to estimate the maximum tolerated dose. Additional patients were enrolled in a dose-expansion part. Regorafenib of 80-160 mg was administered once daily for 21 days on/7 days off with nivolumab 3 mg/kg every 2 weeks. The primary end point was dose-limiting toxicity (DLT) during the first 4 weeks to estimate the recommended dose. RESULTS Fifty patients (25 each with gastric and colorectal cancer) were enrolled. All patients had received $ 2 previous lines of chemotherapy, including anti-angiogenetic inhibitors in 96% of patients. Seven patients with gastric cancer had previously been treated with immune checkpoint inhibitors. One patient had microsatellite instability–high colorectal cancer, whereas the remaining patients had microsatellite stable or mismatch repair–proficient tumors. Three DLTs (grade 3 colonic perforation, maculopapular rash, and proteinuria) were observed with regorafenib 160 mg; none were observed with 80 or 120 mg. During the dose-expansion part, regorafenib dose was reduced from 120 to 80 mg because of frequent maculopapular rash. The common grade $ 3 treatment-related adverse events were rash (12%), proteinuria (12%), and palmar-plantar erythrodysesthesia (10%). Objective tumor response was observed in 20 patients (40%), including 11 with gastric cancer (44%) and 9 with colorectal cancer (36%). Median progression-free survival was 5.6 and 7.9 months in patients with gastric and colorectal cancer, respectively. CONCLUSION The combination of regorafenib 80 mg plus nivolumab had a manageable safety profile and encouraging antitumor activity in patients with gastric and colorectal cancer, which warrants additional investigations in larger cohorts.
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U2 - 10.1200/JCO.19.03296
DO - 10.1200/JCO.19.03296
M3 - Article
C2 - 32343640
AN - SCOPUS:85084466166
VL - 38
SP - 2053
EP - 2061
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 18
ER -
